US5795789A - Standard solution for the determination of thyroid function - Google Patents
Standard solution for the determination of thyroid function Download PDFInfo
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- US5795789A US5795789A US08/868,528 US86852897A US5795789A US 5795789 A US5795789 A US 5795789A US 86852897 A US86852897 A US 86852897A US 5795789 A US5795789 A US 5795789A
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/74—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving hormones or other non-cytokine intercellular protein regulatory factors such as growth factors, including receptors to hormones and growth factors
- G01N33/78—Thyroid gland hormones, e.g. T3, T4, TBH, TBG or their receptors
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S435/00—Chemistry: molecular biology and microbiology
- Y10S435/967—Standards, controls, materials, e.g. validation studies, buffer systems
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T436/00—Chemistry: analytical and immunological testing
- Y10T436/10—Composition for standardization, calibration, simulation, stabilization, preparation or preservation; processes of use in preparation for chemical testing
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T436/00—Chemistry: analytical and immunological testing
- Y10T436/10—Composition for standardization, calibration, simulation, stabilization, preparation or preservation; processes of use in preparation for chemical testing
- Y10T436/106664—Blood serum or blood plasma standard or control
Definitions
- This invention relates to standard solutions containing protein, buffer, stabilizers and analytes adjusted to specific levels for calibration of chemical analyzers.
- this invention relates to a stabilized standard solution for the calibration of clinical assays useful in assessing thyroid function, including total thyroxine, unbound thyroxine, total triiodothyronine, unbound triiodothyronine, and thyroid stimulating hormone.
- the thyroid gland is an endocrine gland located within the neck which synthesizes thyroxine (T 4 ) and also small amounts of triiodothyronine (T 3 ) by incorporation of inorganic iodide into tyrosine residues of thyroglobulin.
- T 4 is the principal circulating thyroid hormone but its effects are mediated after intracellular conversion to T 3 .
- T 4 and T 3 circulate in the blood predominantly bound (>99%) to the serum proteins thyroxine binding globulin (TBG), thyroxine binding prealbumin (TBPA), and albumin.
- TBG serum proteins thyroxine binding globulin
- TBPA thyroxine binding prealbumin
- albumin Some physiologic actions of thyroid hormone include stimulation of metabolism, heart rate, protein synthesis, and carbohydrate metabolism in target tissues.
- the unbound (free) hormone is thought to be the physiologically active form while the protein bound fraction serves as a reservoir of available hormone. This complicates the determination of thyroid status because changes in the levels of binding proteins may lead to an increased total T 4 content in serum without affecting the level of free hormone (e.g. during pregnancy).
- T 4 The production of T 4 is normally regulated by a feedback control loop which includes the hypothalamus and pituitary gland.
- the hypothalamus stimulates the pituitary gland to produce TSH.
- TSH in turn stimulates the production of T 4 by the thyroid gland.
- T 4 production decrease.
- Disruption of the feedback control loop in the hypothalamic-pituitary-thyroid axis leads to non-specific symptoms which can be diagnosed and effectively treated with the aid of laboratory tests.
- Primary hypothyroidism occurs due to destruction of the thyroid gland itself and results in decreased availability of T 4 to tissues.
- TSH hypothyroidism
- Primary hyperthyroidism an oversupply of T 4 to tissues
- Overproduction of TSH also leads to hyperthyroidism. Diagnostic tests aid in the detection of thyroid disease, in determining its mechanism, and in following its treatment.
- Liquid calibration solutions avoid the possibility of inaccurate rehydration of lyophilized calibration materials.
- liquid calibration solutions must contain stabilizers and preservatives that act to increase the useful life and ensure against contaminants.
- Such reagents are known in the industry.
- the requirements placed on the formulation chemist to produce a combination of matrix, analyte, and preservative that are compatible with the analytical system, which can contain the desired concentrations of all desired analytes, and at the same time are able to maintain stability are known to be quite restrictive.
- U.S. Pat. No. 5,342,788 discloses a serum-free standard solution containing TBG, albumin, and buffer. When T 4 or T 3 is added to this solution an equilibrium is established between bound and free hormone resembling that observed in human serum. Stability of the synthetic standard solution was superior to a solution based in human serum and furthermore, bovine TBG afforded superior stability than TBG derived from human serum.
- a remaining shortcoming in the industry involves the addition of multiple thyroid-related analytes within a single liquid calibration solution for use in determination of thyroid function so as to increase flexibility in use as well as reduce production and inventory requirements.
- experience has shown that the simple addition of multiple analytes plus various anti-microbial agents within a single calibration solution would be expected to interfere with the analytical measurement of the other analytes in a sample or to even adversely affect the stability of another analyte in the solution.
- it was an object of the present invention to provide a single, stabilized calibration solution which included known amounts of T 3 , T 4 , free T 4 , free T 3 , and TSH so that the advantages of having a multi-analyte calibration solution could be realized over an extended period of time.
- the present invention is based upon the discovery that a physiologic equilibrium of bound and free thyroid hormones can be established in a single liquid standard or calibration solution containing only albumin as a binding protein without the expected requirement for inclusion of TBG. Consequently, a calibration solution can be formulated simultaneously with specific amounts of triiodothyronine (T 3 ) in combination with specific amounts of thyroxine (T 4 ), which dictate levels of free T 3 and free T 4 , respectively.
- purified TSH is also added to this thyroid hormone calibration solution even though TSH does not circulate in such a bound/free equilibrium so that a multiple-analyte assay calibration protocol may be accomplished using the single calibration solution.
- each one of the analytes has no adverse effect on the utility of the calibration solution in measuring the other analytes nor on the stability of the solution as a whole.
- an extended period of usage or stability of the calibration solution is achieved by including a combination of anti-microbial agents demonstrated to be active against bacteria and fungi and which do not adversely affect the utility of the calibration solution.
- FIG. 1 is a calibration curve for a heterogeneous sandwich immunoassay for TSH using a calibration solution according to this invention.
- FIG. 2 compares the results of a TSH assay using a calibration solution made according to the present invention with results obtained using a known commercial system.
- FIG. 3 is a calibration curve for a competitive hapten immunoassay for free T 4 using a calibration solution according to this invention.
- FIG. 4 compares the results of a free T 4 assay using a calibration solution made according to the present invention with results obtained using a known commercial system.
- FIG. 5 depicts a calibration curve for free triiodothyronine assay using a calibration solution according to this invention.
- FIG. 6 depicts a calibration curve for total triiodothyronine assay using a calibration solution according to this invention.
- FIG. 7 depicts a calibration curve for a total L-thyroxine assay using a calibration solution according to this invention.
- T 4 , T 3 , free T 4 , free T 3 , and TSH are known for determining T 4 , T 3 , free T 4 , free T 3 , and TSH.
- Methods based on immunoassays are particularly useful in a routine clinical setting because automated platforms exist for the performance of these methods. Calibration of these automated platforms involves defining a mathematical relationship between the concentration of the analyte of interest and the detection signal generated. These relationships in immunoassays are commonly non linear such that a system requires multiple standard solutions to define the signal-analyte relationship.
- the calibration solution according to the present invention contains only serum albumin as a protein component.
- the protein serves as an acceptable binding reservoir for both T 4 and T 3 and an acceptable stabilizing milieu for TSH.
- albumin from bovine serum is used as the albumin, although other sources of albumin are acceptable.
- Serum albumin is useful in a range between 40 g/L and 80 g/L which mimics the physiologic protein concentration of serum.
- NaCl is added in a range between 100 and 200 mmoles/L solution.
- the amount of NaCl may vary depending on the sensitivity of the analytical system to ionic strength. If the analytical system is insensitive to ionic strength, NaCl addition may not be required.
- buffers which maintain pH in a range between 6.0 to 8.0 may be required.
- An example of such a buffer is HEPES (N- 2-hydroxyethyl!piperazine-N'- 2-ethanesulfonic add!). If the analytical system is insensitive to pH, the protein component of the matrix may supply all the buffering capacity that is required.
- agents active against contaminating microbes are included in the calibration solution to achieve a desired amount of stabilization.
- agents may consist of any number of compounds which are effective against bacteria and fungi, are inert in the analytical system, and are unreactive towards components of the matrix of the calibration solution and the specific analytes contained therein.
- Polymyxin B is added at a concentration of 0.02 g/L along with sodium pyrithione at a concentration of 0.2 g/L. At these concentrations, Polymyxin B is active mainly against bacteria and sodium pyrithione is active primarily against fungi. It is also useful to add a broad spectrum anti-microbial agent to reinforce the activities of the others.
- 0.1 g/L polyhexamethylene biguanide may be added. This particular combination of agents has been found to be very effective in providing a sterile environment for the calibration solution of the present invention for an extended period of six months or more as discussed hereinafter.
- Thyroxine is preferably added in a range between 0-500 ⁇ g/L, a range which covers the physiologically relevant concentrations found in human serum.
- Exemplary solutions are prepared with thyroxine content of 0, 17, 50, 100, and 400 ⁇ g/L (microgram per deciliter). In the presence of 60 g/L bovine serum albumin, these solutions dictate free thyroxine concentrations of approximately 0, 7, 20, 40, and 160 ng/L (nanogram per liter). Free T 4 measurements are poorly standardized in the diagnostic industry so free T 4 results may vary widely at a given concentration of T 4 depending on the analytical instrumentation.
- Triiodothyronine is preferably used in a range between 0 and 12 ⁇ g/L solution since these concentrations span the physiologically relevant range of triiodothyronine concentrations found in human serum.
- Exemplary solutions are prepared with triiodothyronine content of 0, 1.0, 2.0, 4.0, and 9.0 ⁇ g/L .
- such solutions dictate free triiodothyronine content of approximately 0, 5, 11, 25, and 45 ng/L.
- free T 3 measurements are poorly standardized in the diagnostic industry and the same degree of variation observed in free T 4 analyses may also be seen in free T 3 analyses at any given concentration of T 3 depending on the analytical instrumentation.
- Thyroxine and triiodothyronine have the same structure independent of species so the source of these compounds may vary, also including synthetic material.
- TSH varies according to animal species. Thus, for human diagnosis, TSH derived from humans or synthesized from the human gene sequence is required. TSH does not circulate in a bound/free equilibrium. The amount added is normally completely recovered without the addition of agents which release molecules from binding proteins. TSH is added to an exemplary solution in amounts of 0, 1, 4, 20, and 55 mIU/L (bioactivity units defined by World Health Organization standard material). Amounts of all analytes added are dictated by the relevant physiologic ranges and the requirements for defining a signal vs. concentration response for the specific analytical system.
- T 4 , free T 4 , T 3 , free T 3 , and TSH levels may be formulated depending on specific needs. The only limitations are the interdependence of total hormone levels and the free hormone levels. These cannot be adjusted independently.
- Salt/buffer solution 135 g of NaCl, 89.3 g of HEPES, and 97.5 g of Na-HEPES are dissolved in 15 L of water. Solute and solvent are mixed with a magnetic stirring apparatus until solute is completely dissolved. Mixing for 60 minutes at 25° C. is adequate. This buffer mixture is effective at maintaining the pH of the solution within a range of 7.0 to 8.0, preferably at 7.5.
- Level 1 consists only of preserved matrix and contains none of the analyte substances.
- Levels 2-5 Four other solutions known as the “calibration solutions” (Levels 2-5) are formulated to contain analyte in specific concentrations from low concentrations (Level 2) to high concentrations (Level 5).
- a 50 mg/L stock solution of T 4 is prepared by dissolution of T 4 -sodium salt in 0.05N NaOH. Stock concentration is confirmed using the molar extinction coefficient of T 4 at 325 nm. Dilutions of this stock solution to 5 mg/L and 15 mg/L are prepared in 0.2 g/L bovine albumin solution and are referred to as "working dilutions". These working dilutions are prepared to allow accurate delivery to a specific level of the calibration solution and are formulated 100-200 times the desired final concentration to avoid large dilutions of the calibration solution upon their addition. The working dilutions are added to specified amounts of the preserved matrix to attain final concentrations of 100 and 400 ⁇ g/L of T 4 in levels 4 and 5, respectively.
- Levels 2 and 3 are prepared by dilution of level 4 with appropriate amounts of the preserved matrix to obtain concentrations of 17 ⁇ g/L and 50 ⁇ g/L, respectively.
- Levels 2-5 are mixed for 60 minutes at 25° C. These quantities of T 4 equilibrate between the bound and unbound state in the matrix to result in predictable unbound (free) T 4 concentrations of approximately 7, 20, 40, and 160 ng/L in levels 2, 3, 4, and 5, respectively.
- a stock solution of purified human TSH is prepared by dissolving lyophilized TSH in cold (2°-8° C.) 9 g/L saline.
- Working dilutions containing 100, 400, 2000, and 4400 mIU/L of TSH are prepared in the preserved matrix.
- Levels 2, 3, 4, and 5 are formulated to contain 1.0, 4.0, 20.0, and 55.0 mIU/L TSH, respectively, using the appropriate working dilution.
- Levels 2-5, now containing T 4 and TSH, are mixed thoroughly for 60 minutes at 25° C.
- T 3 sodium salt
- Working dilutions are prepared in a 2 g/L bovine albumin solution containing 200, 400, 800, 1800 ⁇ g/L of T3 and used to formulate levels 2, 3, 4, and 5 containing 1.0, 2.0, 4.0, and 9.0 ⁇ g/L, respectively.
- Levels 2-5, now containing thyroxine, TSH, and T 3 are mixed for 60 minutes at 25° C. These quantities of T 3 equilibrate in the matrix to yield unbound (free) T 3 concentrations of approximately 0, 5, 11, 25, and 45 ng/L in levels 2, 3, 4, and 5, respectively.
- FIG. 1 depicts a calibration curve for a heterogeneous sandwich immunoassay for TSH utilizing the calibration solution according to this invention on a Dimension® RxL Clinical Chemistry System, available from Dade International Inc., (Newark, Del.).
- FIG. 2 demonstrates the accuracy of the calibration solution in FIG. 1. Aliquots from 86 patient sera were measured on the Dimension® RxL Clinical Chemistry System calibrated with standard solution according to this invention and compared with an AXSYM® commercial analytical system calibrated with material and by instructions supplied by its manufacturer, Abbott Laboratories (Abbott Park, Ill.). The data show agreement between the two systems.
- FIG. 3 depicts calibration curves for a competitive hapten immunoassay for free T 4 utilizing the same calibration solution of FIG. 1 according to this invention also using the Dimension® RxL Clinical Chemistry System.
- FIG. 4 demonstrates the accuracy of the calibration solution in FIG. 2. Aliquots from 138 patient sera were measured on the Dimension® RxL Clinical Chemistry System calibrated with standard solution according to this invention and compared with an IMx® commercial analytical system calibrated with material and by instructions supplied by its manufacturer, Abbott Laboratories. The data show agreement between the two systems.
- FIG. 5 depicts a free T 3 calibration curve using a standard solution produced according to the present invention produced on an IMx® commercial system.
- a Total T 3 assay can be performed similarly to free hormone assays by use of an agent which releases T 3 from protein binding sites.
- FIG. 6 depicts a calibration curve for total T 3 using a competitive hapten immunoassay on the IMx® commercial analytical system.
- total T 4 concentrations are large enough in human serum to be determined by immunoassay techniques which do not require a step to concentrate the molecule of interest.
- An example of a total T 4 calibration curve on the Dimension® commercial analytical system made using a calibration solution according to the present invention is shown in FIG. 7.
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Abstract
Description
TABLE ______________________________________ % of analyte recovered after 6 months storage at 2-8° C. in comparison Analyte to storage at -20° C. ______________________________________ Total Thyroxine 99.5% Free Thyroxine 100.8% Total Triiodothyronine 100.4% Free Triiodothyronine 100.4% Thyroid Stimulating Hormone 99.8% ______________________________________
Claims (12)
Priority Applications (6)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US08/868,528 US5795789A (en) | 1997-06-04 | 1997-06-04 | Standard solution for the determination of thyroid function |
JP11502517A JP2000516344A (en) | 1997-06-04 | 1998-05-22 | Standard solution for measurement of thyroid function |
PCT/US1998/010545 WO1998055874A1 (en) | 1997-06-04 | 1998-05-22 | Standard solution for the determination of thyroid function |
DE69812312T DE69812312T2 (en) | 1997-06-04 | 1998-05-22 | STANDARD SOLUTION FOR DETERMINING THE THYROID FUNCTION |
EP98922490A EP0928421B1 (en) | 1997-06-04 | 1998-05-22 | Standard solution for the determination of thyroid function |
ES98922490T ES2194317T3 (en) | 1997-06-04 | 1998-05-22 | STANDARD SOLUTION FOR THE DETERMINATION OF THE THYROID FUNCTION. |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US08/868,528 US5795789A (en) | 1997-06-04 | 1997-06-04 | Standard solution for the determination of thyroid function |
Publications (1)
Publication Number | Publication Date |
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US5795789A true US5795789A (en) | 1998-08-18 |
Family
ID=25351866
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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US08/868,528 Expired - Lifetime US5795789A (en) | 1997-06-04 | 1997-06-04 | Standard solution for the determination of thyroid function |
Country Status (6)
Country | Link |
---|---|
US (1) | US5795789A (en) |
EP (1) | EP0928421B1 (en) |
JP (1) | JP2000516344A (en) |
DE (1) | DE69812312T2 (en) |
ES (1) | ES2194317T3 (en) |
WO (1) | WO1998055874A1 (en) |
Cited By (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6344120B1 (en) | 1999-06-21 | 2002-02-05 | The University Of Hull | Method for controlling liquid movement in a chemical device |
WO2002051403A1 (en) * | 2000-12-21 | 2002-07-04 | Resuscitek, Inc. | Compositions of stable t3 and methods of use thereof |
US20030054571A1 (en) * | 1999-04-30 | 2003-03-20 | Bio-Rad Laboratories, Inc. | Multi-analyte diagnostic test for thyroid disorders |
US6803021B1 (en) | 1998-04-03 | 2004-10-12 | November Ag Novus Medicatus Bertling Gesellschaft Fur Molekulare Medizin | Device for receiving and discharging a given amount of liquid |
US20050059574A1 (en) * | 2000-12-21 | 2005-03-17 | Irwin Klein | Compositions of stable T3 and methodes of use thereof |
US20050249634A1 (en) * | 2004-05-10 | 2005-11-10 | Devlin William J Sr | Calibration solution system for use in an automatic clinical analyzer |
US20060042964A1 (en) * | 2001-08-22 | 2006-03-02 | Sohrab Mansouri | Automated system for continuously and automatically calibrating electrochemical sensors |
US20060094120A1 (en) * | 2004-11-02 | 2006-05-04 | Clark Douglas P | Solution for calibrating a chemical analyzer for alcohol, carbonate and ammonia assays |
US20070178604A1 (en) * | 1999-04-30 | 2007-08-02 | Bio-Rad Laboratories, Inc. | Multi-analyte diagnostic test for thyroid disorders |
US7271009B1 (en) * | 1997-11-18 | 2007-09-18 | Bio-Rad Laboratories, Inc. | Multi-analyte diagnostic test for thyroid disorders |
CN101949941A (en) * | 2010-08-03 | 2011-01-19 | 郑州安图绿科生物工程有限公司 | Kit for detecting total thyroxine by using magnetic particles as solid-phase carriers and preparation method thereof |
EP2356454A2 (en) * | 2008-11-12 | 2011-08-17 | Hemopet | Thyroid analyte detection and measurement |
EP2500076A2 (en) | 2002-04-26 | 2012-09-19 | Abbott Laboratories | Structure and method for handling magnetic particles in biological assays |
CN111103432A (en) * | 2020-01-07 | 2020-05-05 | 郑州安图生物工程股份有限公司 | Freeze-drying auxiliary preparation for thyroid stimulating hormone receptor and freeze-drying method |
CN112269026A (en) * | 2020-09-04 | 2021-01-26 | 首都医科大学附属北京朝阳医院 | Method suitable for accurately preparing TSH powdery international standard substance in concentration |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
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WO2017002751A1 (en) * | 2015-06-29 | 2017-01-05 | 富士レビオ株式会社 | Standard thyroid gland hormone solution |
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1997
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1998
- 1998-05-22 EP EP98922490A patent/EP0928421B1/en not_active Expired - Lifetime
- 1998-05-22 ES ES98922490T patent/ES2194317T3/en not_active Expired - Lifetime
- 1998-05-22 WO PCT/US1998/010545 patent/WO1998055874A1/en active IP Right Grant
- 1998-05-22 JP JP11502517A patent/JP2000516344A/en active Pending
- 1998-05-22 DE DE69812312T patent/DE69812312T2/en not_active Expired - Lifetime
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Cited By (25)
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US7271009B1 (en) * | 1997-11-18 | 2007-09-18 | Bio-Rad Laboratories, Inc. | Multi-analyte diagnostic test for thyroid disorders |
US6803021B1 (en) | 1998-04-03 | 2004-10-12 | November Ag Novus Medicatus Bertling Gesellschaft Fur Molekulare Medizin | Device for receiving and discharging a given amount of liquid |
US7608465B2 (en) | 1999-04-30 | 2009-10-27 | Bio-Rad Laboratories, Inc. | Multi-analyte diagnostic test for thyroid disorders |
US20030054571A1 (en) * | 1999-04-30 | 2003-03-20 | Bio-Rad Laboratories, Inc. | Multi-analyte diagnostic test for thyroid disorders |
US20070178604A1 (en) * | 1999-04-30 | 2007-08-02 | Bio-Rad Laboratories, Inc. | Multi-analyte diagnostic test for thyroid disorders |
US6344120B1 (en) | 1999-06-21 | 2002-02-05 | The University Of Hull | Method for controlling liquid movement in a chemical device |
GB2351245B (en) * | 1999-06-21 | 2003-07-16 | Univ Hull | Method of controlling liquid movement in a chemical device |
US20050059574A1 (en) * | 2000-12-21 | 2005-03-17 | Irwin Klein | Compositions of stable T3 and methodes of use thereof |
WO2002051403A1 (en) * | 2000-12-21 | 2002-07-04 | Resuscitek, Inc. | Compositions of stable t3 and methods of use thereof |
US20060042964A1 (en) * | 2001-08-22 | 2006-03-02 | Sohrab Mansouri | Automated system for continuously and automatically calibrating electrochemical sensors |
US8721852B2 (en) | 2001-08-22 | 2014-05-13 | Instrumentation Laboratory Company | Automated system for continuously and automatically calibrating electrochemical sensors |
US8128801B2 (en) * | 2001-08-22 | 2012-03-06 | Instrumentation Laboratory Company | Automated system for continuously and automatically calibrating electrochemical sensors |
AU2009200931B2 (en) * | 2001-08-22 | 2011-04-21 | Instrumentation Laboratory Company | Method and apparatus for calibrating electrochemical sensors |
EP2500076A2 (en) | 2002-04-26 | 2012-09-19 | Abbott Laboratories | Structure and method for handling magnetic particles in biological assays |
US20050249634A1 (en) * | 2004-05-10 | 2005-11-10 | Devlin William J Sr | Calibration solution system for use in an automatic clinical analyzer |
US20080070309A1 (en) * | 2004-11-02 | 2008-03-20 | Dade Behring Inc. | Solution for calibrating a chemical analyzer for alcohol, carbonate and ammonia assays |
US7294512B2 (en) | 2004-11-02 | 2007-11-13 | Dade Behring Inc. | Solution for calibrating a chemical analyzer for alcohol, carbonate and ammonia assays |
US20060263885A1 (en) * | 2004-11-02 | 2006-11-23 | Clark Douglas P | Solution for calibrating a chemical analyzer for alcohol, carbonate and ammonia assays |
WO2006049999A1 (en) * | 2004-11-02 | 2006-05-11 | Dade Behring Inc. | Solution for calibrating a chemical analyzer for alcohol, carbonate and ammonia assays |
US20060094120A1 (en) * | 2004-11-02 | 2006-05-04 | Clark Douglas P | Solution for calibrating a chemical analyzer for alcohol, carbonate and ammonia assays |
EP2356454A2 (en) * | 2008-11-12 | 2011-08-17 | Hemopet | Thyroid analyte detection and measurement |
EP2356454A4 (en) * | 2008-11-12 | 2012-05-09 | Hemopet | Thyroid analyte detection and measurement |
CN101949941A (en) * | 2010-08-03 | 2011-01-19 | 郑州安图绿科生物工程有限公司 | Kit for detecting total thyroxine by using magnetic particles as solid-phase carriers and preparation method thereof |
CN111103432A (en) * | 2020-01-07 | 2020-05-05 | 郑州安图生物工程股份有限公司 | Freeze-drying auxiliary preparation for thyroid stimulating hormone receptor and freeze-drying method |
CN112269026A (en) * | 2020-09-04 | 2021-01-26 | 首都医科大学附属北京朝阳医院 | Method suitable for accurately preparing TSH powdery international standard substance in concentration |
Also Published As
Publication number | Publication date |
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ES2194317T3 (en) | 2003-11-16 |
EP0928421A1 (en) | 1999-07-14 |
DE69812312T2 (en) | 2004-02-12 |
WO1998055874A1 (en) | 1998-12-10 |
EP0928421B1 (en) | 2003-03-19 |
JP2000516344A (en) | 2000-12-05 |
DE69812312D1 (en) | 2003-04-24 |
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